ORIGINAL ARTICLE
A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer Arunima Gupta, Somnath Roy, Anup Majumdar, Avijit Hazra, Chandrani Mallik
A B S T R A C T
Department of Radiotherapy, IPGMER & SSKM Hospital, Kolkata, West Bengal, India
Address for correspondence: Dr. Somnath Roy, Junior Doctors’ Hostel, Institute of Post Graduate Medical Education & Research (IPGMER) & SSKM Hospital, 242 A.J.C Bose Road, Kolkata – 20, West Bengal, India. E-mail: [email protected]
Background: Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. Aim: This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Materials and Methods: Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m-2 intravenously on day 1 and 5-fluorouracil (1000 mg m-2 continuous intravenous infusion on days 1-4; starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. Results: With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Conclusions: Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions. Key words: Concurrent chemoradiation, esophageal cancer, sequential chemoradiotherapy
Introduction Esophageal carcinoma is a malignancy with a poor prognosis. It is the sixth leading cause of cancer-related death worldwide.[1] Squamous cell carcinoma is still the dominant histology in Asian countries.[2] Only 30% are resectable and 5-year survival is 10% in European studies. Traditionally, carcinoma of the esophagus has been treated by surgery or radiation therapy, but overall 5 year survival Access this article online Quick Response Code:
Website: www.ijmpo.org
DOI: 10.4103/0971-5851.133722
54
rates have been only 5-10%.[3] Most patients with locally advanced esophageal cancer are either not candidates for surgical treatment or prefer not to undergo surgery. Such patients are often treated with chemotherapy and radiation therapy.[4] Primary radiotherapy is usually reserved for patients with extensive locoregional disease that is unresectable or for patients who are not fit to undergo surgery. The combination of chemotherapy involving intravenous (IV) cisplatin and 5-fluorouracil (5-FU) with radiation has further improved outcome for patients with locally advanced disease. Several studies suggested that concurrent chemoradiotherapy (CCRT) would be more beneficial than radiotherapy alone in terms of locoregional control and survival rates for patients with locally advanced disease.[5-9] However, in addition to tumor outcome, toxicity
Indian Journal of Medical and Paediatric Oncology | Jan-Mar 2014 | Vol 35 | Issue 1
Gupta, et al.: Esophageal cancer: sequential vs. concurrent chemoradiation
must also be considered in the framework of overall therapeutic gain. Combining chemotherapy concurrently with radiotherapy runs the risk of intensifying overlapping toxicities. We therefore sought to ascertain whether sequential chemoradiotherapy (SCRT), that is radiotherapy administered sequentially to chemotherapy, would provide efficacy and toxicity outcome comparable to CCRT in the management of locally advanced esophageal squamous cell carcinoma (ESCC). Materials and methods Previously untreated patients with histologically confirmed primary ESCC were recruited from the oncology outpatient department of a tertiary care teaching hospital. The study protocol was approved by the Institutional Ethics Committee and written informed consent was obtained from all the study participants. The eligibility criteria included age 18-70 years, Eastern Cooperative Oncology Group (ECOG) status ≤2, histopathologically proven T1 to T4 ESCC with N1 status (AJCC 2010, Stage IIB and III), hematological and biochemical parameters suitable for radiotherapy or chemotherapy, no tracheoesophageal fistula, no prior chest radiotherapy or chemotherapy or definitive surgery, no other primary cancer and no other diseases that needed hospitalization. The pretreatment assessment included clinical history in detail (including grading of dysphagia) and thorough clinical examination. Acceptable baseline hematological and biochemical parameters included hemoglobin >10 g/dL, leukocyte count >4.0 X 109/mL, platelet count >150 X 109/mL, urea
A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer Arunima Gupta, Somnath Roy, Anup Majumdar, Avijit Hazra, Chandrani Mallik
A B S T R A C T
Department of Radiotherapy, IPGMER & SSKM Hospital, Kolkata, West Bengal, India
Address for correspondence: Dr. Somnath Roy, Junior Doctors’ Hostel, Institute of Post Graduate Medical Education & Research (IPGMER) & SSKM Hospital, 242 A.J.C Bose Road, Kolkata – 20, West Bengal, India. E-mail: [email protected]
Background: Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. Aim: This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Materials and Methods: Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m-2 intravenously on day 1 and 5-fluorouracil (1000 mg m-2 continuous intravenous infusion on days 1-4; starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. Results: With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Conclusions: Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions. Key words: Concurrent chemoradiation, esophageal cancer, sequential chemoradiotherapy
Introduction Esophageal carcinoma is a malignancy with a poor prognosis. It is the sixth leading cause of cancer-related death worldwide.[1] Squamous cell carcinoma is still the dominant histology in Asian countries.[2] Only 30% are resectable and 5-year survival is 10% in European studies. Traditionally, carcinoma of the esophagus has been treated by surgery or radiation therapy, but overall 5 year survival Access this article online Quick Response Code:
Website: www.ijmpo.org
DOI: 10.4103/0971-5851.133722
54
rates have been only 5-10%.[3] Most patients with locally advanced esophageal cancer are either not candidates for surgical treatment or prefer not to undergo surgery. Such patients are often treated with chemotherapy and radiation therapy.[4] Primary radiotherapy is usually reserved for patients with extensive locoregional disease that is unresectable or for patients who are not fit to undergo surgery. The combination of chemotherapy involving intravenous (IV) cisplatin and 5-fluorouracil (5-FU) with radiation has further improved outcome for patients with locally advanced disease. Several studies suggested that concurrent chemoradiotherapy (CCRT) would be more beneficial than radiotherapy alone in terms of locoregional control and survival rates for patients with locally advanced disease.[5-9] However, in addition to tumor outcome, toxicity
Indian Journal of Medical and Paediatric Oncology | Jan-Mar 2014 | Vol 35 | Issue 1
Gupta, et al.: Esophageal cancer: sequential vs. concurrent chemoradiation
must also be considered in the framework of overall therapeutic gain. Combining chemotherapy concurrently with radiotherapy runs the risk of intensifying overlapping toxicities. We therefore sought to ascertain whether sequential chemoradiotherapy (SCRT), that is radiotherapy administered sequentially to chemotherapy, would provide efficacy and toxicity outcome comparable to CCRT in the management of locally advanced esophageal squamous cell carcinoma (ESCC). Materials and methods Previously untreated patients with histologically confirmed primary ESCC were recruited from the oncology outpatient department of a tertiary care teaching hospital. The study protocol was approved by the Institutional Ethics Committee and written informed consent was obtained from all the study participants. The eligibility criteria included age 18-70 years, Eastern Cooperative Oncology Group (ECOG) status ≤2, histopathologically proven T1 to T4 ESCC with N1 status (AJCC 2010, Stage IIB and III), hematological and biochemical parameters suitable for radiotherapy or chemotherapy, no tracheoesophageal fistula, no prior chest radiotherapy or chemotherapy or definitive surgery, no other primary cancer and no other diseases that needed hospitalization. The pretreatment assessment included clinical history in detail (including grading of dysphagia) and thorough clinical examination. Acceptable baseline hematological and biochemical parameters included hemoglobin >10 g/dL, leukocyte count >4.0 X 109/mL, platelet count >150 X 109/mL, urea
